Systemic lupus erythematosus (SLE) is a complex autoimmune disease that presents with a variety of clinical manifestations and affects all races, genders, and age groups. SLE that has onset in childhood tends to be more severe and to have a more aggressive clinical course. Although numerous studies have been performed characterizing the genetics of SLE, none of them have focused on the pediatric-onset subgroup. We have previously collected three cohorts of pediatric SLE patients and matched controls. Clinical data, serum samples, and DNA on most of these subjects are currently available, but no genetic studies on these subjects have been completed to date. At present, over 50 different genes are reported to be associated with SLE in adult populations, and hundreds more represent excellent candidate genes, based on their physiologic functions. We plan to streamline our search for susceptibility genes in pediatric-onset SLE cohorts using the Affymetrix GeneChip, which allows simultaneous genotyping at 10,000 loci and is soon to be expanded to test at 100,000 loci. With assistance from the Data Analysis Core, results from the GeneChip will be correlated with a database of candidate gone loci and known associations and linkages to SLE in adults, as reported in the literature. The top 300 effects, based on a weighting of the significance of the association and the strength of the gene as a candidate for SLE, will be characterized in a second cohort of pediatric-onset SLE cases and controls. It is expected that only a subset of these effects will be confirmed, but those effects that can be replicated are likely to represent true SLE susceptibility loci. Finally, additional SNPs will be typed in each confirmed region to determine the most closely associated haplotype block, which should contain the disease susceptibility mutation itself. Finding such a susceptibility mutation could be useful in predicting disease risk or clinical progression in children with SLE and might be applicable to adult disease, as well. Tracing the biological function of pediatric lupus susceptibility genes and the changes in function that lead to SLE pathogenesis would present an excellent springboard for further work well suited to my background as a molecular biologist and my interest in SLE as a pediatric rheumatologist.